Comparative Transcriptomics Reveals the Role of the Toll-Like Receptor Signaling Pathway in Fluoride-Induced Cardiotoxicity
Autor: | Cailing Wei, Nisha Dong, Xiaolin Tian, Yangang Xing, Xianhui Hao, Xiaoyan Yan, Tong Wang, Yulan Qiu, Jiaxin Xie, Yi Gao, Yi Lv, Jing Feng |
---|---|
Rok vydání: | 2019 |
Předmět: |
Male
0106 biological sciences RNA-Seq 01 natural sciences Rats Sprague-Dawley Transcriptome Fluorides chemistry.chemical_compound Animals Humans Cardiotoxicity Messenger RNA Interleukin-6 Gene Expression Profiling Toll-Like Receptors 010401 analytical chemistry General Chemistry Molecular biology Rats 0104 chemical sciences Toll-like receptor signaling pathway Blot chemistry Apoptosis General Agricultural and Biological Sciences Fluoride Interleukin-1 Protein Binding Signal Transduction 010606 plant biology & botany |
Zdroj: | Journal of Agricultural and Food Chemistry. 67:5033-5042 |
ISSN: | 1520-5118 0021-8561 |
DOI: | 10.1021/acs.jafc.9b00312 |
Popis: | Many studies have shown that fluorosis due to long-term fluoride intake has damaging effects on the heart. However, the mechanisms underlying cardiac fluorosis have not been illuminated in detail. We performed high-throughput transcriptome sequencing (RNA-Seq) on rat cardiac tissue to explore the molecular effects of NaF exposure. In total, 372 and 254 differentially expressed genes (DEGs) were identified between a group given 30 mg/L NaF and control and between a group given 90 mg/L NaF and control, respectively. The transcript levels of most of these genes were significantly down-regulated and many were distributed in the Toll-like receptor signaling pathway. Transcriptome analysis revealed that herpes simplex infection, ECM-receptor interaction, influenza A, cytokine-cytokine receptor interaction, apoptosis, and Toll-like receptor signaling pathway were significantly affected. IL-6 and IL-10 may play a crucial role in the cardiac damage caused by NaF as external stimuli according to protein-protein interaction (PPI) network analysis. The results of qRT-PCR and Western blotting showed a marked decreased mRNA and protein levels of IL-1, IL-6, and IL-10 in the low concentration fluoride (LF) and high concentration fluoride (HF) groups, which was in agreement with RNA-Seq results. This is the first study to investigate NaF-induced cardiotoxicity at a transcriptome level. |
Databáze: | OpenAIRE |
Externí odkaz: |